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Journal of Clinical Medicine Jul 2020Interest in an aetiopathogenic role for in neuropsychiatric diseases started with idiopathic parkinsonism (IP), where the cardinal signs can be assessed objectively.... (Review)
Review
Interest in an aetiopathogenic role for in neuropsychiatric diseases started with idiopathic parkinsonism (IP), where the cardinal signs can be assessed objectively. This systematic review, using an EMBASE database search, addresses Oxford Centre for Evidence-Based Medicine based questions on the inter-relationship of and IP, the benefits of eradicating in IP and the outcome of not treating. The search strategy was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines: 21 of 204 articles met the inclusion criteria. The results show that the assumption that any benefit of eradication results from improved levodopa bioavailability is unjustified. The inter-relationship between and IP is well-established. virulence markers (associated with autoimmunity and immune tolerance) influence the risk, severity and progression of IP. The birth cohort effect for virulence marker antibodies, seen in controls, is obliterated in IP, suggesting causality. Successful eradication in IP is disease-modifying (even in anti-parkinsonian treatment-naïve patients) but not preventive. Hypokinesia regresses with eradication and overall motor severity lessens. Eradication may influence gastrointestinal microbiota adversely, unlocking the next stage in the natural history, the development of rigidity. Failed eradication worsens hypokinesia, as does the presence/persistence of at molecular level only. Adequate prognostic assessment of the consequences of not treating , for IP, is prevented by a short follow-up. We conclude that is a pathophysiological driver of IP.
PubMed: 32650535
DOI: 10.3390/jcm9072159 -
Clinical Endocrinology Oct 2021The imaging of intestinal neuroendocrine tumours (NETs) relies on functional positron emission tomography (PET) tracers; these tumours can be studied by means of both... (Meta-Analysis)
Meta-Analysis
PURPOSE
The imaging of intestinal neuroendocrine tumours (NETs) relies on functional positron emission tomography (PET) tracers; these tumours can be studied by means of both Ga-DOTA peptides and F-fluorodihydroxyphenyl- l-alanine ( F-DOPA) PET/computed tomography (CT). As yet, it is unclear which of these two modalities offers the better sensitivity. We therefore conducted a meta-analysis to assess the available data.
METHODS
PubMed, CENTRAL, Scopus and Web of Science were searched for studies comparing the sensitivity of Ga-DOTA peptides and F-DOPA PET/CT; papers up to February 2021 were considered. In each study, we considered sensitivity in terms of patient-based analysis (PBA), region-based analysis (RBA) and lesion-based analysis (LBA), and pooled the results yielded by each tracer. Multidisciplinary follow-up served as the standard of truth.
RESULTS
Of the 636 records identified, 6 articles published between 2008 and 2021 were finally selected, and 112 intestinal NETs patients were included. The pooled sensitivity of F-DOPA PET/CT was 83%, 89% and 95% on PBA, RBA and LBA, respectively. Ga-DOTA peptides PET/CT showed sensitivity of 88%, 92% and 82% on PBA, RBA and LBA, respectively. No significant differences were found between the two tracers on PBA and RBA. By contrast, a clear trend towards significance in favour of F-DOPA PET/CT was identified on LBA. The presence of a significant difference in favour of F-DOPA PET/CT was confirmed in a subgroup analysis conducted only on the most recent and largest studies. In all three analyses, mild-to-high heterogeneity was found; however, no publication bias was observed.
CONCLUSION
Both F-DOPA PET/CT and Ga-DOTA-peptides PET/CT are reliable diagnostic procedures in patients with intestinal NETs. However, in terms of lesion detection, a non-negligible difference in favour of F-DOPA PET/CT was observed. Thus, the use of F-DOPA PET/CT could be considered as a first-line molecular procedure in intestinal NETs.
Topics: Dihydroxyphenylalanine; Humans; Neuroendocrine Tumors; Organometallic Compounds; Peptides; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography
PubMed: 34018606
DOI: 10.1111/cen.14527 -
Journal of Neurology Apr 2022The best choice between levodopa alone and levodopa sparing medications for early Parkinson's disease (PD) remains controversial. We aimed to evaluate the effect and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The best choice between levodopa alone and levodopa sparing medications for early Parkinson's disease (PD) remains controversial. We aimed to evaluate the effect and safety of levodopa alone and levodopa sparing therapy in symptom relief, neuroimage results and complications.
METHODS
A systematic search was performed in PubMed, The Cochrane Library, EMBASE, and Web of Science for randomized controlled trials of early PD patients comparing levodopa-alone with levodopa-sparing therapy. The mean difference (MD) and the risk ratio (RR) were meta-analyzed.
RESULTS
Twenty-three articles with 4913 patients were included. Significantly greater benefit was detected for the levodopa group in the changes of Unified Parkinson's Disease Rating Scale part II (p < 0.00001), III (p < 0.00001), and total (p < 0.00001) scores, and the between-group MD in part III score increased over time. The loss of the radioligands uptake in levodopa-alone group was also increasingly greater over time. Patients treated with levodopa alone were at higher risk for wearing-off (p < 0.001) and dyskinesia (p < 0.001), but the RR for dyskinesia between the two groups decreased after 2 years of follow-up.
CONCLUSION
Levodopa-alone therapy might be superior in motor symptom relief than levodopa-sparing therapy for early PD patients, and the motor advantage of levodopa-alone might grow over time. Sparing therapy might be associated with less risk of wearing-off and dyskinesia, but the events between the two groups might not be different in the long run. Overall, levodopa alone therapy might bring more net benefit to early PD patients compared with levodopa sparing strategies. The clinical and imaging findings are conflicting, which requires further investigation.
Topics: Antiparkinson Agents; Dyskinesia, Drug-Induced; Humans; Levodopa; Parkinson Disease
PubMed: 34652505
DOI: 10.1007/s00415-021-10830-0 -
Cureus Mar 2023Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This... (Review)
Review
Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This disease is difficult to diagnose since its symptoms are similar to those of the aging process. Those with PD have impaired motor control and function, dyskinesia, and tremors. To treat PD, drugs that enhance the amount of dopamine given to the brain are administered to alleviate symptoms. This inquiry examines the prescription of rotigotine to achieve this objective. The primary objective of this review is to examine the usage of rotigotine in both the late and early stages of PD. The statistical model utilized in the review found that there was not a significant difference in the dosage of rotigotine prescribed to late and early-stage PD patients, however, there were some confounding variables that may have skewed this result; therefore, further research is necessary to validate or nullify this hypothesis.
PubMed: 37069881
DOI: 10.7759/cureus.36211 -
Archives of Gerontology and Geriatrics 2021To identify drug interactions of potentially inappropriate medications and mental and behavioral disorders, according to explicit potentially inappropriate medications... (Review)
Review
OBJECTIVES
To identify drug interactions of potentially inappropriate medications and mental and behavioral disorders, according to explicit potentially inappropriate medications criteria-based tools.
METHODOLOGY
A systematic scoping review was conducted in February 2020. Study characteristics, potentially inappropriate medications, drug interactions, rationale, and therapeutic management proposed were extracted. The commercialization and potentially inappropriate medications standard as essential in Brazil and in the world were identified. Therapeutic management was proposed for the most cited potentially inappropriate medications.
RESULTS
36 tools including 151 drug interactions, in addition to 132 potentially inappropriate medications with concerns related to six mental and behavioral disorders were identified. Cognitive impairment and dementia were the most frequently disorders reported and antipsychotics, anticholinergics, and benzodiazepines were the pharmacological classes more involved in the drug interactions. Despite the tools recommended risperidone and quetiapine when the use of antipsychotics were inevitable; levodopa + carbidopa for Parkinson's disease; and short and intermediate half-life benzodiazepines; the quality of the evidence needs to be assessed. In this review, sleep hygiene; deprescription; medication review; and clinical monitoring of adverse drug reactions are strongly recommended. In addition, to consider agomelatine, bupropion, moclobemide and melatonin as potential safer options for benzodiazepines.
CONCLUSION
Knowing the clinical conditions or risk morbidities associated with the use of potentially inappropriate medications and management of these medications for safer therapeutic equivalents or non-pharmacotherapeutic alternatives are relevant for patient safety.
Topics: Aged; Brazil; Drug Interactions; Humans; Inappropriate Prescribing; Mental Disorders; Potentially Inappropriate Medication List
PubMed: 33227533
DOI: 10.1016/j.archger.2020.104283 -
Journal of Clinical Sleep Medicine :... Apr 2023Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome, but their impact on sleep is still debated, as well the indication for... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome, but their impact on sleep is still debated, as well the indication for treatment. We systematically reviewed the available literature to describe which drug categories are effective in suppressing PLMS, assessing their efficacy through a meta-analysis, when this was possible.
METHODS
The review protocol was preregistered on PROSPERO (CRD42021175848), and the systematic search was conducted on and EMBASE (last searched on March 2020). We included original human studies, which assessed PLMS modification on drug treatment with a full-night polysomnography, through surface electrodes on each tibialis anterior muscle. When at least 4 studies were available on the same drug or drug category, we performed a random-effect model meta-analysis.
RESULTS
Dopamine agonists like pramipexole and ropinirole resulted the most effective, followed by l-dopa and other dopamine agonists. Alpha2delta ligands are moderately effective as well opioids, despite available data on these drugs are much more limited than those on dopaminergic agents. Valproate and carbamazepine did not show a significant effect on PLMS. Clonazepam showed contradictory results. Perampanel and dypiridamole showed promising but still insufficient data. The same applies to iron supplementation.
CONCLUSIONS
Dopaminergic agents are the most powerful suppressors of PLMS. However, most therapeutic trials in restless legs syndrome do not report objective polysomnographic findings, there is a lack of uniformity in presenting results on PLMS. Longitudinal polysomnographic interventional studies, using well-defined and unanimous scoring criteria and endpoints on PLMS are needed.
CITATION
Riccardi S, Ferri R, Garbazza C, Miano S, Manconi M. Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis. . 2023;19(4):811-822.
Topics: Humans; Restless Legs Syndrome; Dopamine Agonists; Nocturnal Myoclonus Syndrome; Movement; Dopamine Agents
PubMed: 36692194
DOI: 10.5664/jcsm.10440 -
Sleep Medicine Dec 2023Augmentation of restless legs syndrome (RLS) is an iatrogenic side effect induced by dopaminergic agents, and it is a major cause of therapeutic failure. Iron deficiency... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Augmentation of restless legs syndrome (RLS) is an iatrogenic side effect induced by dopaminergic agents, and it is a major cause of therapeutic failure. Iron deficiency is a risk factor for RLS, but its effects on the development of RLS augmentation are unclear. This meta-analysis aimed to elucidate the association between serum ferritin and RLS augmentation.
METHODS
We searched the PubMed, Cochrane Library, Embase, ClinicalKey, ScienceDirect, and ProQuest databases for studies comparing the serum ferritin levels of patients with augmented RLS and nonaugmented RLS. A meta-analysis based on a random-effects model was conducted. Levodopa equivalent dose (LED), International Restless Legs Study Group Severity Rating Scale (IRLS), and serum hemoglobin levels were also analyzed.
RESULTS
Six observational studies fulfilled the eligibility criteria of this meta-analysis. A total of 220 RLS patients with augmentation and 687 RLS patients without augmentation were included. The results revealed that augmented RLS was significantly associated with low serum ferritin levels (p = 0.002), high LEDs (p = 0.026), and nonsignificantly associated with high IRLS scores (p = 0.227).
CONCLUSIONS
A low serum ferritin level is associated with RLS augmentation. For patients with RLS who are iron deficient, iron supplements can not only relieve their fundamental RLS symptoms but also lower the risk of RLS augmentation. Moreover, non-dopminergic agents should be considered as the first-line treatment for patients with persistent low serum ferritin levels or those with moderate to severe RLS to prevent augmentation.
Topics: Humans; Restless Legs Syndrome; Dopamine Agents; Levodopa; Iron; Ferritins; Observational Studies as Topic
PubMed: 37879259
DOI: 10.1016/j.sleep.2023.10.022 -
European Journal of Nuclear Medicine... Feb 2024Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [I]-metaiodobenzylguanidine (mIBG) is the standard imaging method;...
BACKGROUND
Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals.
METHODS
We searched the PubMed database for studies performing a head-to-head comparison between [I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([C]C-HED), F-18F-3,4-dihydroxyphenylalanine ([F]DOPA) [I]mIBG and Meta-[18F]fluorobenzylguanidine ([F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA).
RESULTS
Ten studies were selected: two regarding [C]C-HED, four [F]DOPA, one [I]mIBG, and three [F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies.
CONCLUSIONS
PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.
Topics: Child; Humans; 3-Iodobenzylguanidine; Dihydroxyphenylalanine; Neuroblastoma; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 37962616
DOI: 10.1007/s00259-023-06486-9 -
Movement Disorders : Official Journal... Aug 2021Advanced Parkinson's disease is inconsistently defined, and evidence is lacking in relation to device-aided therapies. To update existing reviews of intrajejunal... (Review)
Review
Advanced Parkinson's disease is inconsistently defined, and evidence is lacking in relation to device-aided therapies. To update existing reviews of intrajejunal infusion of levodopa/carbidopa (LCIG), we performed a literature search for relevant articles (to November 3, 2020) using PubMed supplemented by hand searching. Retrieved articles were categorized by relevance to identified research questions, including motor complications and symptoms; nonmotor symptoms; functioning, quality of life, and caregiver burden; optimal timing of treatment initiation and administration duration; discontinuation; and complications. Most eligible studies (n = 56) were open-label, observational studies including relatively small patient numbers. LCIG consistently reduces OFF time and increased ON time without troublesome dyskinesia with varying effects regarding ON time with troublesome dyskinesia and the possibility of diphasic dyskinesia. More recent evidence provides some increased support for the benefits of LCIG in relation to nonmotor symptoms, quality of life, activities of daily living, and reduced caregiver burden. Patient age does not appear to significantly impact the effectiveness of LCIG. Discontinuation rates with LCIG (~17%-26%) commonly relate to device-related issues, although the ability to easily discontinue LCIG may represent a potential benefit. LCIG may be a favorable option for patients with advanced Parkinson's disease who show predominant nonmotor symptoms and vulnerability to complications of other advanced therapy modalities. Larger, well-controlled studies, including precise investigation of cost effectiveness, would further assist treatment selection. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Activities of Daily Living; Antiparkinson Agents; Carbidopa; Drug Combinations; Gels; Humans; Levodopa; Parkinson Disease; Quality of Life
PubMed: 33899262
DOI: 10.1002/mds.28595 -
Neuroscience Letters Mar 2022As an adenosine receptor A2A antagonist, istradefylline is used as an adjunctive agent of levodopa to improve motor symptoms in advanced Parkinson's disease (PD)... (Meta-Analysis)
Meta-Analysis
As an adenosine receptor A2A antagonist, istradefylline is used as an adjunctive agent of levodopa to improve motor symptoms in advanced Parkinson's disease (PD) patients. In this study, we re-evaluated the effects of istradefylline on treating the motor symptoms of PD patients. We performed a literature search up to November 2021 from electronic databases. Eligible studies were synthesized for efficacy, tolerability, OFF time, Unified Parkinson's Disease Rating Scale part III score, ON state with dyskinesia, and the incidence of treatment-emergent adverse events. As a result, nine clinical studies with 2727 subjects on istradefylline treatment for PD patients were included. Our results showed that compared to placebo, istradefylline exhibited a statically significant difference in efficacy (1.39 [1.15 to 1.69]; p = 0.001), decreasing OFF time (-0.58 [-1.01 to - 0.16]; p = 0.007), and improving ON state with dyskinesia (0.69 [0.02 to 1.37]; p = 0.043). For tolerability, UPDRS III, and adverse effects, there was no significant difference between istradefylline and placebo. In conclusion, the results suggest that istradefylline exhibits an efficient and well-tolerated role in treating PD patients. Randomized controlled trials and long-term studies are still required to investigate the effects of istradefylline on motor and non-motor symptoms of PD in future research.
Topics: Adenosine A2 Receptor Antagonists; Antiparkinson Agents; Dyskinesias; Humans; Levodopa; Parkinson Disease; Purines; Treatment Outcome
PubMed: 35149201
DOI: 10.1016/j.neulet.2022.136515